The burden of typhoid fever in low- and middle-income countries: A meta-regression approach

Background: Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. Methods: We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. Results: We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9–48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2–4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. Conclusions: Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases. Author summary: Typhoid fever is a bacterial enteric infection that continues to pose a considerable burden to the 5.5 billion people living in low- and middle-income countries (LMICs). We developed and validated a model incorporating widely available indicators of economic and social development and the environment to estimate the burden of typhoid fever across LMICs. Our analysis uses all available data to estimate the incidence of typhoid in key age groups, which is important for the design and implementation of optimal vaccination strategies, and it identifies regions of the world that have the most uncertainty in typhoid incidence. Across all LMICs, we estimated that the expected number of typhoid fever cases per year is 17.8 million (95% CI: 6.9–48.4 million). We also present the probability that incidence surpasses the criteria for low, medium, high, and very high incidence in each country, which could help guide policy in the face of uncertainty.